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Sci China Life Sci. 2018 Feb 10. doi: 10.1007/s11427-017-9156-1. [Epub ahead of print]
The S190R mutation in the hemagglutinin protein of pandemic H1N1 2009 influenza virus increased its pathogenicity in mice.
Chen Y1,2, Bai T1,2, Zhu W1,2, Gao R1,2, Deng Z3, Shi Y4, Zou S1,2, Huang Y3, Li X1,2, Li F3, Feng Z1,2, Chen T1,2, Yang J1,2, Wang D1,2, Gao L5, Shu Y6,7,8.
Author information
Abstract
Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients' respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.
KEYWORDS:
HA mutation; egg adaptation; mice; pandemic H1N1 2009 influenza virus; pathogenicity; receptor binding domain
PMID: 29445999 DOI: 10.1007/s11427-017-9156-1
The S190R mutation in the hemagglutinin protein of pandemic H1N1 2009 influenza virus increased its pathogenicity in mice.
Chen Y1,2, Bai T1,2, Zhu W1,2, Gao R1,2, Deng Z3, Shi Y4, Zou S1,2, Huang Y3, Li X1,2, Li F3, Feng Z1,2, Chen T1,2, Yang J1,2, Wang D1,2, Gao L5, Shu Y6,7,8.
Author information
Abstract
Human influenza viruses preferentially bind to sialic acid-α2,6-galactose (SAα2,6Gal) receptors, which are predominant in human upper respiratory epithelia, whereas avian influenza viruses preferentially bind to SAα2,3Gal receptors. However, variants with amino acid substitutions around the receptor-binding sites of the hemagglutinin (HA) protein can be selected after several passages of human influenza viruses from patients' respiratory samples in the allantoic cavities of embryonated chicken eggs. In this study, we detected an egg-adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and evaluated the effects of this mutation on receptor binding affinity and pathogenicity in mice. Our results revealed that residue 190 is located within the pocket structure of the receptor binding site. The single mutation to arginine at position 190 slightly increased the binding affinity of the virus to the avian receptor and decreased its binding to the long human α2,6-linked sialic acid receptor. Our study demonstrated that the S190R mutation resulted in earlier death and higher weight loss in mice compared with the wild-type virus. Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi were observed in the lung tissues of mice infected with the mutant virus.
KEYWORDS:
HA mutation; egg adaptation; mice; pandemic H1N1 2009 influenza virus; pathogenicity; receptor binding domain
PMID: 29445999 DOI: 10.1007/s11427-017-9156-1